1. Field of the Invention
This invention relates to a process for preparing polyvinylpyrrolidone-iodine (PVP-I.sub.2), and, more particularly, to a method of making a stable, low K-value, water-soluble PVP-I.sub.2 in the form of a uniform, free-flowing powder.
2. Description of the Prior Art
The reaction product of PVP with elemental iodine, known as PVP-iodine, or PVP-I.sub.2, is marketed as a brown powder which contains about 11% of available iodine, i.e. active iodine, which can be titrated with sodium thiosulfate, and, in addition, contains about 5.5% of iodine in the form of iodide. At an iodine:iodide ratio of 2:1, the iodine bonding in the PVP-iodine complex is so strong that an iodine odor is no longer perceptible and a moist potassium iodide/starch paper introduced into the gas space above the PVP-iodine no longer acquires a color. In practice, the measure employed to assess whether the iodine is sufficiently firmly bonded is the partition coefficient of the iodine between an aqueous PVP-iodine solution and heptane, and this coefficient, as described, for example, in U.S. Pat. No. 3,028,300, should be about 200. Further it is necessary that in its formulations, in particular in aqueous solution, the PVP-iodine should lose very little available iodine on storage, i.e. it should be very stable.
Very diverse measures have been described for the preparation of a stable PVP-iodine. For example, according to German Pat. No. 1,037,075, the pulverulent PVP-iodine was subjected to a lengthy heat after-treatment at 90.degree.-100.degree. C.; while U.S. Pat. No. 2,900,305 proposed using a PVP having a defined moisture content for the preparation of a suitable PVP-iodine. U.S. Pat. No. 2,826,532 disclosed the addition of sodium bicarbonate; and U.S. Pat. No. 3,028,300 the addition of iodide in the form of hydrogen iodide or of an alkali metal iodide. U.S. Pat. No. 3,898,326 proposed the addition of hydrogen iodide or of an alkali metal iodide to an aqueous PVP solution, followed by reaction of the pulverulent PVP-iodide mixture, obtained from the solution after drying, with iodine. German Published Application DAS 2,439,197 stated that polyvinylpyrrolidone polymerized in an anhydrous organic solvent was particularly suitable for the preparation of a stable PVP-iodine.
The above prior art processes are also intended to permit economical preparation of a stable PVP-iodine. However, they also suffer from substantial disadvantages. According to the process described in German Pat. No. 1,037,075, for example, heating for from 18 to 64 hours at 90.degree.-100.degree. C. to form the PVP-iodine complex was necessary to obtain a stable product having an iodine:iodide ratio of 2:1. The process described in U.S. Pat. No. 2,900,305 entailed heating PVP and iodine for 22 hours at 90.degree.-100.degree. C.
According to U.S. Pat. No. 3,028,300, heating can be dispensed with if iodide in the form of an alkali metal iodide or hydriodic acid is added to the mixture of polyvinylpyrrolidone and iodine. This process, however, does not represent an optimum, since inhomogeneous mixtures are formed, in which the iodine is only weakly bonded, and, accordingly a strong smell of iodine is present. A related process without heat treatment was proposed in U.S. Pat. No. 3,898,326 wherein iodides, e.g. as HI or NaI, were added to an aqueous polyvinylpyrrolidone solution, drying, and the pulverulent polyvinylpyrrolidone/iodide mixture reacted with iodine. However, HI causes corrosion problems on drying, while NaI increase the alkali content above the stringent requirements of the drug laws. German Published Application DAS 2,439,197 suggested a heating time of 10 hours; however to achieve a partition coefficients of about 200 it was necessary to heat for at least 20 hours.
The heating times can be greatly reduced, as disclosed in German Published Application DAS 2,818,767, PVP is reacted with elementary iodine in the presence of formic or oxalic acids, or an ammonium salt or amide of carbonic acid, formic acid or oxalic acid.
U.S. Pat. No. 4,402,937 described the preparation of the product in water rather than the solid state. The process comprised reacting PVP with elemental iodine in the presence of formic acid, oxalic acid or an ammonium salt or amide of carbonic acid, formic acid or oxalic acid, in aqueous solution.
These and other methods, however, have not provided a process for making stable, PVP-iodine complexes having a K-value of about 10-20 which are water-soluble, uniform, free-flowing powders. Accordingly, it is the object of the present invention to provide a process for the preparation of such product.
These and other objects and features of the invention will become apparent from the following description.